ABSTRACT: The long-term goal of our research remains the same, i.e., to learn how the brain generates sympathetic nerve discharge (SND) under basal conditions and formulates complex and highly differentiated cardiovascular response patterns that accompany behavioral and pathophysiological states such as alerting, defense, and neurogenic hypertension. The central theme of the research proposed here revolves around the hypothesis that the 10-Hz and 2- to 6-Hz rhythms in SND reflect functionally distinct modes of operation of the brain stem system governing the cardiovascular state of the cat. Specifically, we propose that the 10-Hz rhythm reflects the ability of coupled brain stem oscillators to formulate a variety of complex and highly differentiated patterns of spinal sympathetic outflow, each suited to a particular behavioral need. For example, one such pattern leads to a shift in blood flow from visceral to skeletal muscle vascular beds as occurs during the fight or flight reaction. As a corollary, we propose that the 2- to 6-Hz rhythm reflects the ability of the same system to generate a uniform level of background activity (i.e., tone) in all components of the spinal sympathetic outflow. These proposals will be tested by measuring the discharges of sympathetic nerves innervating different organs in conjunction with femoral, mesenteric and renal blood flows in unanesthetized-decerebrate cats. Differential changes in regional blood flows produced by stimuli known to elicit defense or REM sleep-like states will be correlated to changes in sympathetic nerve power and/or pattern (i.e., rhythm). Additional specific aims of the proposal are: 1) to identify those brain stem regions responsible for the 10-Hz rhythm in SND, 2) to characterize the neurons with activity correlated to 10-Hz SND in these regions, 3) to define the interconnections of these neurons so as to formulate a circuit wiring diagram, 4) to determine whether the 10-Hz rhythm arises from brain stem pacemaker neurons or whether this rhythm is an emergent property of a network oscillator, and 5) to test the hypothesis that switching between the 10-Hz and 2- to 6-Hz rhythms in SND is dependent upon a balance between the activities of cholinergic and noradrenergic brain stem neurons. Approaches to these problems include the use of spike-triggered averaging and frequency-domain analysis (i.e., coherence) to identify single brain stem neurons with activity correlated to 10-Hz SND, antidromic mapping of the axonal projections of such neurons (for circuit diagram construction) and spike train analysis to distinguish pacemaker and non-pacemaker neurons with activity correlated to 10-Hz SND.